Hydrogen peroxide-mediated protein oxidation in young and old human MRC-5 fibroblasts

It is suggested that the aging process is dependent on the action of free r adicals. One of the highlights of age-related changes of cellular metabolis m is the accumulation of oxidized proteins. The present investigation was u ndertaken to reveal the proliferation-related changes in the protein oxidat ion and proteasome activity during and after an acute oxidative stress. It could be demonstrated that the activity of the cytosolic proteasomal system declines during proliferative senescence of human MRC-5 fibroblasts and is not able to remove oxidized proteins in old cells efficiently. Whereas in young cells removal of oxidized proteins was accompanied by an increase in the overall protein turnover, this increase in protein turnover could not b e seen in old MRC-5 fibroblasts, Therefore, our studies demonstrate that ol d fibroblasts ape much more vulnerable to the accumulation of oxidized prot eins after oxidative stress and are not able to remove these oxidized prote ins as efficiently as young fibroblasts. (C) 2000 Academic Press.